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. 2020 Dec 11;18(1):475.
doi: 10.1186/s12967-020-02636-x.

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Xiao-Li Wei  1 , Xuan Luo  2 , Hui Sheng  3 , Yun Wang  4 , Dong-Liang Chen  1 , Jia-Ning Li  5 , Feng-Hua Wang  6 , Rui-Hua Xu  7   8
Affiliations

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Xiao-Li Wei et al. J Transl Med. .

Abstract

Background: The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.

Methods: 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity.

Results: The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03-0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases.

Conclusions: The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.

Keywords: Colorectal cancer; Liver metastases; PD-L1; Primary tumor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Association of PD-L1 expression with CD4 density and CD8 density in liver metastasis in CRC. Positive PD-L1 expression in liver metastasis is significantly related with higher levels of CD4 density and CD8 density in liver metastasis in CRC
Fig. 2
Fig. 2
Representative immunostaining of PD-L1, CD4 and CD8 in primary tumor a–c and paired liver metastatic tumor (d–f). a PD-L1 expression in primary tumor with a CPS score of 5.5; b CD4 density in primary tumor with a percentage of 40%; c CD8 density in primary tumor with a percentage of 22.5%; d PD-L1 expression in liver metastasis with a CPS score of 20; e CD4 density in liver metastasis with a percentage of 40%; f CD8 density in liver metastasis with a percentage of 20%
Fig. 3
Fig. 3
Comparisons of PD-L1 expression between primary tumors and liver metastasis in subgroups of CRC. PD-L1 expression (assessed using CPS scoring) was significantly higher in liver metastasis compared with primary colorectal tumors in the patients with concurrent resection of primary and metastatic tumors (n = 56) subgroup, but not in metachronous resection subgroup
See this image and copyright information in PMC

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